World Library  
Flag as Inappropriate
Email this Article

Rti-177

Article Id: WHEBN0023641979
Reproduction Date:

Title: Rti-177  
Author: World Heritage Encyclopedia
Language: English
Subject: RTI-120, 2α-(Propanoyl)-3β-(2-(6-methoxynaphthyl))-tropane, FE-β-CPPIT, FP-β-CPPIT, 2β-Propanoyl-3β-(2-naphthyl)-tropane
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Rti-177

RTI-177
Systematic (IUPAC) name
5-[(1R,2S,3S,
Clinical data
Legal status
?
Identifiers
ATC code ?
PubChem
ChEMBL  YesY
Chemical data
Formula C24H25ClN2O 
Mol. mass 392.92 g/mol

RTI-177 (2β-(3-phenylisoxazol-5-yl)-3β-(4-chlorophenyl)tropane, β-CPPIT) is a synthetic stimulant drug from the phenyltropane family, which acts as a DRI with micromolar affinity for the SERT.[1] RTI-177 has an unusually long duration of action of 20 hours or more, substantially longer than the related compound RTI-336 from which it differs in molecular structure only by the absence of a p-methyl group.[2]

"the nonselective monoamine transporter inhibitor RTI-126 and the DAT-selective inhibitors RTI-150 and RTI-336 both had a faster rate of onset (30 min) and a short duration of action (4h). In contrast, the nonselective monoamine transporter inhibitor RTI-112 had a slower rate of onset (30–60 min) and a longer duration of action (10h). The DAT-selective inhibitors RTI-171 and RTI-177 also had slower rates of onset (30–120 min), but RTI-171 had a short duration of action (2.5 h) while RTI-177 had a very long duration of action (20 h)."[3]

Update

Lower reinforcing strength of the phenyltropane cocaine analogs RTI-336 and RTI-177 compared to cocaine in nonhuman primates.

Comparison of six MAT inhibitors

RTI X R [3H]CFT [3H]Nisoxetine [3H]Paroxetine
Coc 89.1 3298 (1986) 1045 (45)
177 Cl phenyl 1.28 504 (304) 2420 (220)
176 Me phenyl 1.58 398 (239) 5110 (465)
354 Me ethyl 1.62 299 (180) 6400 (582)
336 Cl p-cresyl 4.09 1714 (1033) 5741 (522)
386 Me p-anisoyl 3.93 756 (450) 4027 (380)

In the Lindsey paper, RTI-177 was wrongly considered to be a dual inhibitor of the NET, although this was later found out to be incorrect (despite being written in plain English).

"In acute toxicity studies in male rats, 3β-(4-chlorophenyl)-2β-[3-(4’-methylphenyl)isoxazol-5-yl]tropane (RTI-336) possessed an LD50 of 180 mg/kg after oral administration, compared with 49 mg/kg for RTI-177 (unpublished results, Howell 2005; Table 9). These results suggested that RTI-336 was a better candidate than RTI-177 for further preclinical development."[2]

Also the potency of the heterocyclic compounds is not as great as would be predicted based on in vitro test results.

References

  1. ^ [1] Lindsey, K.P., Wilcox, K.M., Votaw, J.R., Goodman, M.M., Plisson, C., Carroll, F.I., Rice, K.C., Howell, L.L. Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: relationship to transporter occupancy determined by positron emission tomography neuroimaging. Journal of Pharmacology and Experimental Therapeutics, 309: 959-969, 2004.
  2. ^ a b [2] Carroll FI, Howard JL, Howell LL, Fox BS, Kuhar MJ. Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse. AAPS J. 2006 Mar 24;8(1):E196-203.
  3. ^ [3] Kimmel HL, O'Connor JA, Carroll FI, Howell LL. Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys. Pharmacol Biochem Behav. 2007 Jan;86(1):45-54.
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 



Copyright © World Library Foundation. All rights reserved. eBooks from World eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.